CC BY
30
Section 5. Medical science
Abduzhabarova Zulfiya Murathodzhaevna, Assistant of the Department of Pediatrics, Tashkent Institute of Advanced Medical
E-mail: zulfiya.m@mail.ru
Profile immunogeneticheskie children with celiac disease Uzbek population
Abstract: The study involved 54 children with celiac disease Uzbek population aged 1 to 14 years. The diagnosis was verified on the basis of criteria ESPGAN. The positive association of HLA genes with D DQA1 * 0501, HLA DQV1 * 0201, HLA-DRV1 * 07 and * 13. For children, having allele DRB1 * 16 and DQA1 * 0501 is set at high risk for the disease refractory to carriers of alleles DRB1 * 12 — high risk of atypical forms of the disease.
Keywords: genetics, children, celiac disease, HLA-class II of.
Celiac disease (CD) at children one of actual problems of clinical pediatrics, owing to growth of its prevalence, tendency to recuring, and it is frequent also to the progressing current with development of the complicated forms conducting to an invalidization. Comprehension of her multisystem essence and development effective the serologicheskikh of tests have allowed to elicit the fact that the celiac disease meets much more often. Celiac disease — a disease with hereditary predisposition and the greatest risk of her development is observed in the presence of HLA-DQ2 and HLA-DQ8 of geterodi-mer which are defined more than 90 % of patients in Europe and the USA. Connection between development of CD and presence at sick some anti-genes of HLA system II of a class is established. Most often gap-lotipa of DR3, DR7, DQ2 meet. And, paramount value as it is found more than in 90 % of patients in Northern Europe is allocated for the last gaplotip. Approximately his same frequency (95 %) occurs at the Russian children, and ethnic Kazakhs have 62 % [1; 2; 3]. Heterodimeasures of DQ2 it is revealed at all Indian children, haplo-type by DR3-at 34.28 % [4]. In Chile at patients with CD prevailed haplotype DQ8; at sick bedouins the same gaplotipa, as in the European population — DQ2 and DQ8 are revealed [5]. The Brazilian researchers have revealed high connection with development of a disease of alleles of DRB1 * 03,* 07 and DQV1 * 02 [6].
The role ofvarious genes of HLA in definition of clinical results of a gluten enteropatiya is up to the end not studied. But such research, in our opinion, is important and necessary as allows to obtain new data on mechanisms of communication of HLA system and CD, to open new opportunities for more exact individual forecast ofpredisposition to CD, her prevention and the choice of treatment.
Search of associative communications of products of HLA with diseases begins as the rule, from the comparative analysis of features of a HLA phenotype of ill and healthy faces within one population. Therefore we have considered it expedient to study features of polymorphism of genes of a HLA II class in group of patients with CD.
Materials and methods
We have examined 54 children from CD Uzbek population aged from 1 till 14 years, middle age has made 7.3 ± 1.9 years, boys 27 (50 %) was girls 27 (50 %). The diagnosis was verified on the basis of criteria of ESPGAN. Separate allelic options of genes of HLA-DRB1, by HLA-DQA1 and HLA-DQB1 have been analysed and nature of distribution of spetsifichnost of a HLA II class of loci of DRB1 *, by DQA1 *, DQB1 * is studied. The class HLA-2 which
are responsible for hereditary predisposition to C defined PTsR — method in the St. Petersburg Medico-genetic Center (Candidates of Medical Science N. V. Vokhmyanina). The control group was made by 109 children of Uzbeks [10].
Results and discussion
Children with C have a frequency of occurrence of alleles, HLA-DRB1 * 07 and * 13 was much higher, than in control group (tab. 1). At the same time at patients authentically less than in control, the HLA-DRB1 * 15 option tipirovatsya that demonstrates possible protective participation of these alleles in pathogenesis of development of Ts. Risk of development of CD in the persons having DR7 options in the genotype it is revealed, at 60 % of patients. The greatest criterion of reliability was defined for alleles of DRB1 *07 and * 13. Thus, specific predisposition to CD is associated with HLA-DRB1 * 13 at children of the Uzbek population.
DQA1 locus DQA1 * 0102 allele negatively are associated with CD and it allows to consider her as CD protectors. The maximum value relative rice and criterion of reliability is noted for allele by DQA1 * 0501, i. e. it positively is associated with CD (h2 = 7.28, RR = 2.03). We have also established that alleles of DQA1 * 0501 expressed at 66.6 % of sick Ts. U of North Americans this indicator has made 97 % of patients, Russians — 90, at ethnic Kazakhs have 26.4 % [3; 7; 8].
The criterion of reliability and relative risk at sick children with DQB1 * 0201 (x2 = 6.74, RR = 1.97), i. e. he positively are associated with CD and can be considered as a marker of predisposition to CD. low values of relative risk and high rates of criterion of reliability from preventive fraction (RR = 0.16; x2 = 3.95; PF = 4.95) in the presence allele DQB1 * 0303, demonstrate possible protective action of this allele.
The high risk of development of a disease was inherent in carriers with different combinations of alleles: DQA1 * 0102, * 0501 and DQV1 * 0201. The combination of pathological alleles of DQA1 * 0501 and DQV1 * 0201 is associated with the molecule DQ2; DQA1 * 0301 and DQV1 * 0302 — with the molecule DQ8.
Similar to other populations at our patients authentically more often than at healthy children, DQ2 heterodimeasures (88 %) met, and in every second case they were coded by genes in situation a trance. DQ8 came to light in 9 % of cases that by 4 times more often than at Europeans and, so his presence specifies, on high risk of hereditary predisposition to C.
Profile immunogeneticheskie children with celiac disease Uzbek population
Note: further on in this document: n — number of alleles in this selection; X — criterion of reliability; P — an importance indicator by exact criterion of Fischer; Rs — a reliability indicator according to Pearson; EF — etiologichesky fraction; PF—preventive fraction, RR — relative risk.
Table 2. - Frequency of occurrence of spetsifichnost of a HLA II class at patients with a celiac disease depending on a phenotype and the course of a disease
Table 1. - Frequency of occurrence of spetsifichnost of a HLA II class at patients from celiac disease Uzbek population
Allele DRB1 * Sick, n = 54 Control, n = 109
n x2 P Pc EF PF RR n GF
DRB1 *07 11 3.88 0.03 0.04 0.12 2.17 24 0.11
DRB1 * 12 2 1.53 0.19 0.21 0.02 2.98 3 0.01
DRB1 * 13 14 6.52 0.01 0.01 0.17 2.53 29 0.13
DRB1 * 15 3 3.85 0.02 0.05 1.94 0.31 38 0.17
HLA DQA1
* 0101 11 2.97 0.03 0.08 0.79 0.54 34 0.17
* 0102 11 4.01 0.02 0.04 0.94 0.49 34 0.19
* 0501 36 7.28 0.01 0.17 2.03 39 0.19
HLA DQB1
* 0201 36 6.74 0.01 0.16 1.97 41 0.20
* 0303 1 3.95 0.03 0.04 4.99 0.16 12 0.05
* 0503 4 1.86 0.12 0.17 0.02 2.75 3 0.01
Allele DRB1 Typical form, n = 41 Control n = 109
n x2 P Pc EF PF RR n GF
* 07 9 4.80 0.01 0.02 0.17 2.78 24 0.11
* 13 13 13.16 0.01 0.0002 0.281 4.03 29 0.13
Allele DQA1
* 0102 6 5.95 0.06 0.014 1.69 0.34 34 0.19
* 0501 29 7.60 0.002 0.005 0.195 2.22 39 0.19
Allele DQB1
* 0201 32 11.18 0.01 0.23 2.53 41 0.20
* 0301 8 2.17 0.05 0.14 0.76 0.54 29 0.16
* 0303 1 2.64 0.07 0.10 3.55 0.21 12 0.05
* 0502 2 3.97 0.02 0.04 2.83 0.24 14 0.09
Allele DRB1* Aty pical form, n = 13
* 10 1 2.21 0.21 0.13 0.08 4.73 5 0.02
* 11 2 0.76 0.22 0.38 0.10 2.02 24 0.11
* 12 1 4.12 0.15 0.04 0.09 7.96 3 0.01
Allele DQA1
* 0101 3 0.45 0.22 0.50 0.09 1.57 34 0.17
* 0201 2 0.30 0.27 0.58 0.05 1.54 25 0.14
Allele DQB1
* 0302 2 0.36 0.26 0.54 0.06 1.61 24 0.11
* 0503 1 3.22 0.17 0.07 0.07 6.51 3 0.01
* 0601 1 0.89 0.29 0.34 0.05 2.74 7 0.03
Allele DRB1 Refractory current, n = 7
*15 2 2.96 0.12 0.085 0.39 4.89 38 0.17
*16 1 17.09 0.05 3.65 0.24 36 2 0.01
Allele DQA1
* 0102 3 0.06 0.25 0.808 0.03 1.17 34 0.19
* 0201 2 0.10 0.28 0.749 0.03 1.28 25 0.14
* 0501 6 4.22 0.03 0.039 0.28 3.05 39 0.19
Allele DQ1
* 0301 3.33 0.23 2.80 29 0.16
* 0302 0.14 0.03 1.34 24 0.11
Thus, at persons of the Uzbek population the positive association C with HLA DQA1 genes * 0501, HLA DQV1 * 0201, HLA-DRV1 * 07 and * 13 is established.
Studying of a carriage of alleles of HLA of genes of the II class at children with a typical form of a disease has shown that
the frequency of occurrence of alleles of DRB1 * 07 and * 13, DQA1 * 0201 and * 0501 was higher, than in control (tab. 2) that corresponds the published data and point to positive association of it allele with CD [9]. DQA1 allele * 0102 and DQB1 * 0502 was much higher, than in control (x2 = 5.95; PF = 1.69) and (x2 = 3.97;
PF = 2.83) that demonstrates protective participation of it allele in pathogenesis of CD.
At an atypical form the frequency of occurrence of alleles of DRB1 * 12, was higher, than at healthy. In the analysis of polymorphism of groups of alleles of a gene of DRB1 at children with a refractory current of CD the frequency of occurrence of an allele of DRB1 * 16 considerably exceeded control indicators. The high risk of development of a refractory course of a disease is established at DQA1 * 0501 and DRB1 * 16 carriers.
Thus, at our patients the positive association CD with genes of HLA DQA1 * 0501, HLA DQB1 * 0201, HLA-DRB1 * 07 and * 13 is established. For the children having an allele of DRB1 * 16 and DQA1 * 0501 the high risk of development of a refractory course of a disease, for carriers of alleles DRB1 * 12 — high risk of development of an atypical form of a disease is established. We regarded existence of HLA DRB1 * 12 as ethnic feature of the Uzbek population and the evidence of her participation in pathogenesis of development of an atypical form of a disease.
References:
1. Kondrateva E. I., Yankina G. N., Loshkova E. V. Clinical and immunological features of celiac disease in children//Problems of Tomsk. children. dietetics. - Moskva, 2007. - № 1. - P. 66.
2. Mashkeev A. K., Karsybekova L. M., Sharipova M. N. Celiac disease in children. - Almaty, 2008. - P. 240.
3. Vokhmyanin N. V. Genetic aspects of celiac disease: a review//Med. genetics. - M., 2010. - №1. - P. 3-8.
4. Kaur G., Sarkar N., Bhatnagar S. Pediatric celiac disease in India is associated with mul-tiple DR3-DQ2 haplotypes//Hum. Immunol. - 2002. - 8(63). - P. 677-682.
5. Neuhausen S. L., Weizman Z., Camp N.J. HLA DQ1-DQB1 genotypes in Bedouin families with celiac disease//Hum. Immunol. -2002. - 6(63). - P. 502-507.
6. Silva E. M., Fernandes M. I., Galvro L. C. Human leukocyte antigen class II alleles in white Brazilian patients with celiac disease//J. Pe-diatr. Gastroenterol. Nutr. - 2000. - 4(31). - P. 391-394.
7. Celiac disease - state of the art. Conclusion The US team of experts//[Electronic resource]. - Available from: http://consensus.nih. gov/cjns/118/118celiac.htm (Final statiment - August 09.2004/National instinutes of health consensus development conference statiment on celiac disease - June 28-30, 2004).
8. Isabekova T. K. Clinical and epidemiological features and organization leche-of celiac disease in children: Author. Dis. ... Cand. honey. Sciences. - M., 2008. - P. 24.
9. Loshkova E. V. Genetic and immunologic mechanisms of cus-cal manifestations of celiac disease in children and adolescents and their importance in rehabilitation: Av-toref. Dis. .Cand. honey. Sciences. - M., 2009. - P. 23.
10. Ruzibakieva M. R. Molecular subtype polymorphism HLA II class in the pain-governmental chronic hepatitis with cirrhosis of the «C» of the liver - viral etiology in the Uzbek population: Author. Dis. ... Cand. honey. Sciences. - Tashkent, 2007. - P. 20.
Abdushukurov Abdurashid, Research Institute of Epidemiology, Microbiology and Infectious Diseases, candidate of medical sciences Gulyamov Nariman, doctor of medical sciences, professor Ruzmetov Dilshod, candidate of medical sciences Akhmedova Khalida, doctor of medical sciences E-mail: akhmedova1957@mail.ru
The influence of immonumoduline on the effectiveness of vaccination of typhoid fever
Abstract: In 162 male volunteers aged 18-22 years, studied the efficacy of typhoid vaccines adsorbed liquid chemical production of "Uzbiofarm" Immunomodulin and influence on the process of antibody production.
Vaccinated receiving typhoid vaccine the formation of a protective level of antibodies was observed in 61.6 %, whereas 38.4 % of the vaccine did not contribute to the formation of protective antibody titers and was not effective. In the group vaccinated and received simultaneously Immunomodulin formation of a protective antibody titer was observed in 95.2 % of those with a lack of protective antibody titers — at 4.8 %. Immunomodulin contributed to the intensification of antibody production and a significant increase in the effectiveness of typhoid vaccine.
Low efficiency of typhoid vaccine was due to low levels of neutrophils in the blood additional activation NBT-test. The intensification of the process of antibody production under the influence of Immunomodulin was mediated through its effect on inducing functionally metabolic activity of blood neutrophils in response to a vaccine antigen.
Keywords: typhoid fever, typhoid vaccines, Immunomodulin, NBT-test, functionally metabolic activity ofblood neutrophils.
